Salmonella-Based Oral Vaccine Prevented Diabetes in Nonobese Diabetic Mice

BOSTON — A Salmonella Typhimurium bacteria, in combination with cytokines and a low dose of the immunosuppressive drug Anti-CD3, restored normal glucose tolerance and prevented type 1 diabetes in nonobese diabetic mice.

Additionally, the combination therapy significantly increased the regulatory cytokines IL10 and IL2, and inhibited the inflammatory IFNγ. Taken together, the results suggest that the vaccine suppressed autoimmunity mechanisms and increased regulatory mechanisms.

Based on these results, the researchers concluded that a Salmonella-based oral vaccine expressing autoantigens in combination with tolerogenic cytokines and subtherapeutic dose of Anti-CD3 is a promising therapy for the prevention of type 1 diabetes.

“The current standard of care is to treat the symptom, high blood sugar levels and its consequences, without addressing the underlying autoimmunity,” Mohamed I. Husseiny Elsayed, PhD, assistant research professor at the Beckman Research Institute of City of Hope, said in a press release. “This vaccine is a very safe and effective targeted immunotherapy and we believe it’s a great place to start in the development of a vaccine to stop type 1 diabetes.”

Dr Husseiny Elsayed presented the results at ENDO 2016.

Researchers developed an oral vaccine for type 1 diabetes based on live attenuated Salmonella using the mouse preproinsulin (mPPI) gene as the autoantigen fused to SseF effector protein of type-III secretion system (T3SS) encoded by Salmonella Pathogenicity Island-2 (SPI2) under the control of the intracellular regulated promoter. The SPI2-T3SS of Salmonella is only expressed inside of antigen-presenting cells (APCs), allowing preferential delivery of fused protein into the APC cytosol for optimal immunogenicity.

The Salmonella-based delivery of autoantigen was co-administered with Salmonella-based delivery of DNA for mammalian expression of TGFβ or IL10 by the host APCs.

Researchers found that oral vaccination in combination with mPPI+TGFβ or mPPI+TGFβ+IL10 prevented diabetes in nonobese diabetic mice and restored normal glucose tolerance. Dr Husseiny Elsayed and his colleges also noted similar efficacy using another diabetic autoantigen, glutamic acid decarboxylase (GAD)-65, with TGFβ.

Reference

1. Husseiny Elsayed MI. LBSUN-46. Salmonella-Based Combination Immunotherapy for Type 1 Diabetes. Presented at: ENDO 2016; April 1-4, 2016; Boston, MA.